This proposal will investigate the modulatory role of auditory centrifugal pathways including the olivocochlear (OC) efferent system. There are two Specific Aims. Aim 1 will investigate the role of lateral efferents in excitotoxic damage induced by acoustic overstimulation. The effects of lesioning lateral efferents on sound-induced swelling of radial afferent dendrites and shifts in the auditory nerve compound action potential (CAP) threshold tuning curve will be examined. It will also be determined if intracochlear applications of lateral efferent neurotransmitters prevent swelling of radial dendrites and shifts in CAP threshold tuning curve induced by acoustic overstimulation. Finally, the effects of lateral efferent lesions on levels of efferent neurotransmitters in the organ of Corti will be measured. Aim 2 will establish the modulatory role of centrifugal pathways using GABA and glycine as neurotransmitters on acoustic processing in the cochlear nucleus (CN). The effects of lesioning and stimulating centrifugal pathways on the spontaneous levels, sound- evoked forward masking functions and tuning properties of CN neurons will be determined. The effects of efferent lesions on GABA and glycine levels and release in the CN using in vivo microdialysis and immunocytochemical techniques will also be determined. Finally, the effects of GABA and glycine agonists and antagonists on spontaneous levels, forward masking functions and tuning of CN neurons will be measured. The results of these studies will provide information on the functional role of centrifugal efferent systems in the auditory neuraxis and a better understanding of how the brain influences hearing and hearing disorders.